Abstract 2937: Animal models for evaluating the efficacy of anti-human HER2 ADC alone or in combination with IO therapy

Abstract Antibody-drug conjugates (ADCs) combine the targeting ability of antibodies with the killing power of cytotoxins, allowing for the release of highly toxic payloads within tumor cells, thereby enhancing therapeutic efficacy while reducing systemic toxicity. ADCs have demonstrated significant efficacy as monotherapy in the treatment of various tumors. However, like many cytotoxic agents, the issue of drug resistance limits the sustained efficacy they can achieve as standalone treatments. To overcome this challenge, the combined application of ADCs with other therapies is becoming a new focus of research. Among these, the combination of immuno-oncology inhibitors (IO) with ADCs has shown strong therapeutic potential in clinical settings. An appropriate preclinical evaluation model can effectively assess the therapeutic potential of ADCs. Biocytogen developed a HER2-expressing MC38 cell line called B-hHER2 MC38 plus. The HER2 expression level of B-hHER2 MC38 plus is similar to that of the human cell line NCI-N87, and it can form tumors normally in B-hHER2 mice. In a syngeneic transplantation model of B-hHER2 mice with MC38 plus cells, the anti-HER2 antibody-drug conjugate (ADC) analogous to trastuzumab, MMAE, exhibited a dose-dependent tumor suppression effect. When combined with the anti-mPD-1 antibody, it demonstrated a higher tumor suppression rate. In another syngeneic transplantation model where B-hHER2 MC38 plus cells were inoculated into B-h4-1BB/hHER2 mice, the commercial product DS8201 showed significant tumor growth inhibition. In the xenograft models using a diverse array of human tumor tissues - including breast cancer tumor tissues (BP0818 and BP1056), colorectal cancer tumor tissues (BP0170 and BP0847), lung cancer tumor tissues (BP0508 and BP0638), as well as breast cancer cell lines (BT-474 and MDA-MB-231), and the gastric cancer cell line (NCI-N87) - the commercial product DS8201 demonstrated significant tumor growth inhibition. Citation Format: Jean Huang, Chong Li, Ruili Lv, Qinjun Wang, Qingqing Xu, Heling Shen, Xiaofei Zhou. Animal models for evaluating the efficacy of anti-human HER2 ADC alone or in combination with IO therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2937.